Masking the taste of compositons containing salt

ABSTRACT

The invention relates to the use of sweeteners for masking the salty taste of compositions as well as compositions containing salt and defined sweeteners, the amount of sweeteners being suitable for masking the salty taste of the composition.

The present invention relates to the use of sweeteners for masking thesalty taste of compositions and relates to compositions containing salt,which contain defined sweeteners, the quantity of sweetener beingsuitable to mask the salty taste of the composition.

Sodium Chloride as an Active Ingredient in Therapy

Sodium chloride is used in diverse ways and used in various medicinalforms as an active ingredient for therapeutic purposes. In parenteralmedicinal forms, such as, for example, infusion solutions, sodiumchloride is used for electrolyte replacement. Sodium chloride is sprayedas an isotonic solution for inhalation in order to moisten therespiratory tracts.

Moreover, sodium chloride is an ingredient of glucose-electrolytepreparations, so-called oral rehydration salt (ORS) solutions. ORSsolutions are applied orally for electrolyte and volume replacement. Thepreparations are packed portion-wise in sachets as a powder mixture.Before use, the powder is completely dissolved in a prescribed quantityof water. Finished preparations are, for example, Santalyt®, Elotrans®,Infectodiarrstop® or Oralpädon® 240. The preparations are frequentlyprescribed in paediatric therapy in order to ensure rehydration and anadequate electrolyte balance in diarrhoea disorders.

A drawback of these preparations is that, owing to the presence ofsodium chloride, an aqueous ORS solution tastes salty. Furtherconstituents are, inter alia, potassium chloride, which reinforces thesalty taste of the solutions. The salty taste may lead to complianceproblems. One aim in the development of pharmaceutical agents should beto make the taking of pharmaceutical agents as pleasant as possible. Amasking of the salty taste should be aimed for pharmaceutical agentswith a definite salty taste in order to avoid compliance problems.

New WHO Guideline for ORS Solutions

The World Health Authority (WHO) issued a new guideline on ORS solutionsin 2002. Because of new clinical study results, the concentrations ofNa⁺, Cl⁻ and glucose have been reduced. As a consequence, the totalosmolarity of the solutions has been reduced from 311 mosmol/l to 245mosmol/l. Table 1 lists the old and new WHO recommendations from 1969and 2002.

TABLE 1 Old and new WHO guidelines on the composition of ORS solutionsElectrolyte/glucose Old (1969) New (2002) Na⁺ 90 mmol/l 75 mmol/l K⁺ 20mmol/l 20 mmol/l Cl⁻ 80 mmol/l 65 mmol/l Glucose 111 mmol/l 75 mmol/lCitrate³⁻ 10 mmol/l 10 mmol/l Osmolarity 311 mosmol/l 245 mosmol/l

Table 2 lists the molar fractions of exemplary preparations.

TABLE 2 Molar fractions of the components in finished pharmaceuticalagents Constituent Preparation A Preparation B Preparation C Na⁺ 60mmol/l 60 mmol/l 60 mmol/l K⁺ 20 mmol/l 20 mmol/l 20 mmol/l Cl⁻ 50mmol/l 60 mmol/l 60 mmol/l Glucose 111 mmol/l 90 mmol/l 90 mmol/lCitrate³⁻ 10 mmol/l 10 mmol/l 10 mmol/l Total 251 mosmol/l 240 mosmol/l240 mosmol/l Osmolarity

The European Society of Paediatric Gastroenterology and Nutrition(ESPGAN) also recommend a hypotonic composition for ORS solutions with60 mmol/l sodium. The osmolarity should be in the region of 200 to 250mosmol/l. The ESPGAN recommends a smaller maximum limit for theosmolarity than the WHO.

Addition of Sweeteners to ORS Solutions

It is known to add sweetening agents to compositions containing salt,such as ORS solutions, for example. Sweetening agents include sugar,sugar alcohols and sweeteners. Sugars contribute to the energy balanceof the body. The energy value of one gram of saccharose is 16.8 kJ.Sugars promote caries of the teeth. Insulin is required for themetabolisation of most sugars. They contribute to the total osmolarityof a solution. The sweetening power of sugar is small in comparison tosweeteners. Saccharose has a sweetening power of one. The sweeteningpower of each sweetening agent is related to the value one ofsaccharose. The sugar alcohols include sorbitol, maltitol, maltitolsyrup, mannitol, isomalt, lactitol and xylitol. They are similar tosugars in taste. The sweetening power compared to saccharose is lower inall sugar alcohols. Sugar alcohols hardly contribute to the energybalance of the body. No insulin is consumed for metabolisation. Thedevelopment of caries is not promoted. If sugar alcohols are taken inlarge quantities, diarrhoea and bloating may occur.

Sweeteners differ from sugars and sugar replacements with respect tomany points. Regardless of the substantially higher sweetening powercompared to sugars and sugar alcohols, sweeteners do not have aninfluence on the insulin level or on the digestion system or dentalhealth. No insulin is consumed. No diarrhoea is produced. No cariesoccurs. Sweeteners have practically no calories influencing the energybalance. Currently, eight sweeteners are permitted in the European Unionin food law. The sweeteners are listed in Table 3. An E number isprovided for each sweetener and an ADI value is defined. The “acceptabledaily intake” (ADI) value gives the quantity in milligrams per kilogramof body weight (KG) of the substance, which can be taken daily for lifewithout incurring damage.

TABLE 3 Sweeteners permitted in the European Union Sweetening Sweetenerpower E number ADI value/kg KG Acesulfame potassium 200 E 950 15 mgAspartame 200 E 951 40 mg Aspartame-acesulfame 350 E 962 40 mg/15 mgsalt Sodium cyclamate 30 E 952 11 mg Neohesperidin 1000 E 959  5 mgdihydrochalcone Saccharin sodium 500 E 954  5 mg Sucralose 600 E 955 15mg Thaumatin 3000 E 957  5 mg

The sweeteners are very heterogeneous with respect to their structure.They may be artificially produced compounds or compounds obtained fromnatural products. Artificial sweeteners are, for example, aspartame,acesulfame-K, Na-cyclamate or saccharin-Na. They are frequently presentin a salt form in order to increase solubility in water. Theaspartame-acesulfame salt consists of 64% aspartame and 36% acesulfame.A synergy in an increase of the sweetening power relative to theindividual materials is achieved by the combination of the sweeteners.In the human organism, the aspartame-acesulfame salt is split into itsoriginal components aspartame and acesulfame. Acesulfame is eliminatedunchanged via the kidneys. Aspartame is metabolised in the body.Aspartame is a phenylalanine source. If aspartame is contained in aproduct, the safety indication “This product contains a phenylalaninesource” has to be printed on the packaging. The aspartame-acesulfamesalt is marketed under the trade name Twinsweet®. Other sweeteners areof natural origin. Neohesperidin dihydrochalcone is a flavonoidderivative made of the peel of citrus fruits. Thaumatin is obtained fromthe West African katem fruit Thaumatococcus daniellii. Thaumatin is anatural protein. Two further sweeteners, steviosid and neotam arecurrently being checked for approval. Steviosid is obtained from theleaves of the plant Stevia Rebaudina Bertoni. The plant comes from SouthAmerica. Steviosid has a sweetening power of 100 to 150. Neotam is anaspartame derivative. It has better hydrolytic stability. The sweeteningpower is about 10,000.

All previously known compositions containing salt (sometimes alsocontaining sweetener), for example ORS, have the disadvantage asmentioned above, however, that they sometimes involve a very unpleasantsalty taste, and this makes use significantly more difficult inpaediatrics, in particular.

To this extent, the present invention is based on the object ofproviding a means for masking the salty taste of compositions containingsalt. The present invention is based on the further object of providinga composition containing salt without an unpleasant salty taste, i.e. acomposition in which the salty taste is masked as completely aspossible. It is additionally an object of the invention to mask thesalty taste of a composition which corresponds to the new WHO guidelinesfor ORS solutions.

These objects are achieved by the subject of the independent claims.Preferred embodiments are given in the sub-claims.

The present invention is based on the surprising recognition that theuse of at least one sweetener from the group of sodium cyclamate,aspartame or acesulfame potassium is suitable for masking the saltytaste of a composition. Although the individual sweeteners have alreadybeen used individually or in combination in preparations containingsalt, this took place purely for the purpose of sweetening thepreparation. Nothing was hitherto known of the suitability for maskingthe unpleasant salty taste and the quantities of sweetener hitherto usedwere also not adequate for this purpose.

Without wanting to be bound to a theory, the hitherto most plausibleexplanation for the surprising effect of sodium cyclamate, aspartame oracesulfame potassium on the taste perception of salty substances ispossibly an influencing or competition of the signal transmission fromtaste receptors. Because the receptors for the sodium cation and therespective anions are structurally very different from those of therelevant sweetener, a direct inhibitory reciprocal effect at thereceptors is improbable. However, it could be the case that thesubstances released after the receptor stimulation (“second messengers”)of sweet and salty taste perception influence one another or that thebrain can no longer distinguish between the two taste impressionsbecause of similar signal transmitter substances.

Possibly, the stimulation of taste cells by sodium ions ensures adepolarisation of the cells resulting in an intracellularly increasingcalcium concentration. The three sweeteners according to the inventionactivate a receptor which empties calcium stores by means of themessenger inositol triphosphate, and this also leads to an increase inthe intracellular calcium concentration in the same cells.

To this extent, the present invention relates, according to a firstaspect, to the use of at least one sweetener from the group of sodiumcyclamate, aspartame or acesulfame potassium, for masking the saltytaste of a composition.

It has been shown according to the invention that in particular acombination of more than one of these sweeteners entails advantageous,synergistic effects. The quantity of the individual sweetener can bedisproportionately reduced by the use of a combination of sweeteners andtherefore the recommended highest daily doses for the individualsweeteners can be adhered to without problems (even in paediatrics). Therequired masking of taste is retained. In the case of the composition,according to the claims, of the ORS solutions, the total osmolarityrecommended by the WHO is not exceeded despite the addition ofsweetener.

To this extent, according to a preferred embodiment, a mixture of two orthree of the above-mentioned sweeteners is used for masking taste.

As already mentioned, some salt-containing preparations, which alsocontain sweeteners as the sweetening agent, already exist. These were,however, added in doses, which are not suitable for masking the saltytaste. The inventors have now found that the above-mentioned sweetenersin particular produce a masking of taste when they are used above adefined concentration threshold.

This concentration of the sweetener is calculated according to apreferred embodiment by the formula:

relative sweetening power of the sweetener×mass of the sweetener[inmg]>5,000

By way of example, in the case of Na-cyclamate as the only addedsweetener, the following relationship would be produced (see also Table3):

30×quantity Na-cyclamate[mg]>5,000

Thus the quantity of Na-cyclamate, which at least has to be used inorder to (on its own) achieve a masking of taste, >166.66 mg. Thisquantity is generally based on a salt content of the composition ofabout 0.77 g, in other words about 0.7 to 0.8 g. With a larger quantityof salt, the sweetener quantity has to be corresponding increased.

These salts are primarily the salts NaCl and KCl used in, for example,ORS or other electrolyte compositions. Another salt, the taste of whichcan be masked is, for example, sodium-3-hydroxybutyrate. In principle,the taste of all salts can be masked, insomuch as it is perceived assalty. This is not the case, for example, for sodium citrate, whichproduces only a sour taste perception. Understandably, no masking of thesalty taste can be achieved here either. In the case of sodium benzoate,which is at the same time perceived as bitter and salty, the salty tastecomponent can be masked but the bitterness is then perceived just asmuch or even increasingly.

According to the invention, Na-cyclamate can preferably be used in aconcentration of 22 to 28, preferably 26% by weight, based on the saltcontent of the composition. This concentration only applies toapplication on its own (without the addition of further sweeteners).

For aspartame and acesulfame potassium, in the case of use on their own,a concentration of 3.3 to 4.5, preferably 3.9% by weight based on thesalt content of the composition is produced.

As already stated above, it is particularly advantageous to use amixture of two or three of the above-mentioned sweeteners, theconcentration of the sweetener mixture based on the salt content beingcalculated as follows:

rel. sweetening power Na-cyclamate×mass Na-cyclamate[in mg]+

rel. sweetening power aspartame×mass aspartame[in mg]+

rel. sweetening power acesulfame-K×mass acesulfame-K[in mg]>5,000

based on a salt content of the composition of 0.7 to 0.8, preferably0.77 g.

Preferred combinations are, in particular:

-   -   a) Na-cyclamate/acesulfame-K    -   b) Na-cyclamate/aspartame, or    -   c) acesulfame-K/aspartame.

These are particularly preferably used in the following concentrations(in % by weight), based on the salt content:

-   -   a) 3.2/3.2    -   b) 3.9/3.2    -   c) 2.6/2.6

As already mentioned at an earlier point, in particular the taste ofNaCl and/or KCl are to be masked.

The composition, in which the sweetener(s) is used, is preferably apharmaceutical composition, a foodstuff or a food supplement. Thepharmaceutical composition is, in particular, an electrolyte composition(ORS). The foodstuff or the food supplement is preferably an electrolytedrink.

According to a second aspect, the present invention comprises acomposition containing salt, which contains at least one sweetener fromthe group of sodium cyclamate, aspartame or acesulfame potassium, thequantity of sweetener being suitable to mask the salty taste of thecomposition.

The composition preferably contains a mixture of two or three sweetenersfor masking the taste. The concentration of the sweeteners based on thesalt content is calculated as given above by the formula:

relative sweetening power of the sweetener×mass of the sweetener[inmg]>5,000

based on a salt content of the composition of 0.7 to 0.8, preferably0.77 g.

Na-cyclamate, aspartame and acesulfame potassium are preferably used inthe composition in the concentrations given above.

A mixture of two or three of the sweeteners is preferably used in thecomposition, the concentration of the sweetener mixture based on thesalt content being calculated as follows:

rel. sweetening power Na-cyclamate×mass Na-cyclamate[in mg]+

rel. sweetening power aspartame×mass aspartame[in mg]+

rel. sweetening power acesulfame-K×mass acesulfame-K[in mg]>5,000

based on a salt content of the composition of 0.7 to 0.8, preferably0.77 g.

The composition preferably contains the following sweetenercombinations:

-   -   a) Na-cyclamate/acesulfame-K    -   b) Na-cyclamate/aspartame, or    -   c) acesulfame-K/aspartame,        preferably in the concentrations given above.

With respect to the salts contained in the composition, see also theabove statements.

The composition according to the invention is preferably apharmaceutical composition, a foodstuff or a food supplement.

The term “pharmaceutical composition”, as used herein primarily means apharmaceutical agent, in which electrolytes (together with thesweeteners according to the invention) are present in a quantity, whichis suitable for the respective treatment purpose, for example for thesupportive treatment in the case of diarrhoea disorders. Thecomposition, in this case, also contains additional constituents such asglucose (see below), but also taste correctives, flavourings etc.

The pharmaceutical composition is preferably an electrolyte composition,preferably an ORS (oral rehydration salt) preparation.

The composition is alternatively a (dietary) foodstuff or a foodsupplement in the form of an electrolyte drink.

A pharmaceutical composition may, in addition to the one or moresweeteners, have the following ingredients:

Constituent Concentration [g]/Single dose Glucose 3.56 Sodium chloride0.47 Potassium chloride 0.3 Disodium hydrogen citrate-1,5 hydrate 0.53

The present invention will now be illustrated by the following examplesand figures. In the figures:

FIG. 1 shows results of the taste test of the finished preparation Bwithout sweetener and flavouring.

FIG. 2 shows results of the taste test of the finished preparation Bwith the sweetener aspartame and strawberry flavouring.

FIG. 3 shows results of the taste test of the finished preparation Bwith the sweetener aspartame and apple-banana flavouring.

FIG. 4 shows results of the taste test of the finished preparation Cwithout flavouring and with the sweetener aspartame.

FIG. 5 shows results of the taste test for the sweetener combinationacesulfame-K/Na-cyclamate.

FIG. 6 shows results of the taste test for the sweetener combinationaspartame/Na-cyclamate.

FIG. 7 shows results of the taste test for the sweetener combinationacesulfame-K/aspartame.

FIG. 8 shows results of the taste test with regard to the salty taste ofthree sweetener combinations and orange dry flavouring.

FIG. 9 shows results of the taste test of the three sweetenercombinations with the flavouring addition pineapple.

FIG. 10 shows results of the taste test of the three sweetenercombinations with the flavouring addition lemon.

FIG. 11 shows results of the taste test of the three sweetenercombinations with the flavouring addition orange.

FIG. 12 shows results of the taste test of the three sweetenercombinations with the flavouring addition raspberry.

FIG. 13 shows results of the taste test of the three sweetenercombinations with the flavouring addition apple.

FIG. 14 shows results of the taste test of the sweetener combinationacesulfame-K/aspartame with the flavouring addition raspberry.

FIG. 15 shows results of the taste test of the sweetener combinationacesulfame-K/aspartame with the flavouring addition lemon.

EXAMPLES

Permitted sweeteners were used for a taste test on ORS solutions.Different concentrations of 10 to 200 mg of the sweetener Na-cyclamatewere weighed into the solids mixture. Na-cyclamate is a sodium salt likeNaCl. In comparison to other sweeteners, it has a low sweetening power.It was to be found out whether the salty taste of the ORS solution canbe masked as a function of concentration by Na-cyclamate. The powdermixtures were weighed out according to the composition of the WHO anddissolved in water according to the instruction.

After organoleptic checking, no salty taste was perceived for the ORSsolution with a concentration of 200 mg Na-cyclamate. A complete maskingof taste had been achieved. The concentration of 200 mg Na-cyclamate wasestablished as the standard concentration, with which a complete maskingof taste can be achieved.

It was to be tested with the other sweeteners whether a comparablemasking is possible. It was to be investigated whether by adding asweetener with comparable sweetening, a masking of taste can also beachieved. The sweeteners were calculated to the standard concentrationof the Na-cyclamate. The different sweetening power values of thesweeteners were used as the reference variable. Comparableconcentrations could be calculated with a multiplication factor based onthe sweetening power of the individual sweeteners. The concentrationsare listed in Table 2.

TABLE 2 Concentrations of the sweeteners based on the standardconcentration of 200 mg Na-cyclamate Sweetening Sweetener quantitySweetener power Factor [mg] Na-cyclamate 30 1 200 Acesulfame-K 200 0.1530 Aspartame 200 0.15 30 Acesulfame-aspartame salt 350 0.09 18Saccharin-Na 500 0.06 12 Sucralose 600 0.05 10 Neohesperidin 1000 0.03 6dihydrochalcone Thaumatin 3000 0.01 2

The calculated quantities of sweeteners were added to the ORS powdermixtures and dissolved in water. The following organoleptic test tookplace.

The salty taste of the ORS solutions could not be masked in a similarmanner by any further sweetener concentration, as by the addition of 200mg Na-cyclamate. The perception of the salty taste was different betweenthe individual ORS solutions. The salty taste was perceived to a lesserextent by the addition of acesulfame-K, aspartame, theacesulfame-aspartame salt. Only a small to no improvement could beachieved by the remaining sweeteners. The sweet taste of thaumatin couldonly be perceived delayed by seconds. The salty taste of the ORSsolution was immediately perceived and could also no longer be masked bythe delayed sweet perception of the thaumatin.

After standardisation of the solutions to a comparable sweetness by theabove-mentioned sweeteners, a comparable masking could be achieved.

Sweetener Combinations

An aim of the present invention is to mask as completely as possible thesalty taste of ORS solutions. The fact has been investigated that anaddition of certain sweeteners leads to a masking or at least animprovement of the salty taste. A masking was achieved with thesweeteners Na-cyclamate, acesulfame-K, and aspartame. An attempt is tobe made with the three sweeteners to improve the masking of the saltytaste of ORS solutions.

An addition of sweeteners is not possible to unlimited extent (at leastwith regard to the current guidelines). ADI values (acceptable dailyintake) were established for the sweeteners. Using the ADI values,maximum concentrations can be calculated, which may be applied daily bya substance without incurring damage for life. The sweetener addition tothe ORS solutions is limited by the ADI values. According to thespecialist information for preparation C, the therapeutic maximum doseis four sachets a day for babies and small children. As Na-cyclamate hasan ADI value of 11 mg per kg of bodyweight, an addition of 200 mgNa-cyclamate per dose is too much. Table 3 lists the permissible highestdaily doses for sweeteners, which may be applied daily. The calculationrelates to the bodyweight of a child weighing 10 kg.

TABLE 3 Highest daily doses of sweeteners calculated to their ADI valuesADI value [mg/kg Highest daily dose/10 kg Highest Sweetener BW] BW[mg]dose/sachet [mg] Na-cyclamate 11 110 27.5 Acesulfame-K 15 150 37.5Aspartame 40 400 100.0 Saccharin-Na 5 50 12.5

The sweetener addition is limited by the ADI values. An addition of 200mg Na-cyclamate per dose of an ORS solution exceeds the permissiblehighest daily limit for a child weighing 10 kg by about twice theamount. The masking of the salty taste of ORS solutions is not possibleby the addition of an individual sweetener. It is investigated whether amasking of the salty taste can be achieved by the addition of sweetenercombinations to the constituents of an ORS solution.

When developing a pharmaceutical agent, as few auxiliary materialsshould be used as possible. Possible incompatibilities between theactive ingredient and auxiliary material or intolerances in the patientto a constituent of the formulation are limited to a minimum.

In order to use as few sweeteners as possible, two sweeteners from Table3 are combined with one another in each case. The result is sixcombinations. In order to mask the salty taste as successfully aspossible, the concentrations of the sweeteners were selected to be closeto the maximum daily highest limit, acesulfame-K 30 mg, Na-cyclamate 25mg, saccharin-Na 10 mg. As aspartame has the comparatively highest ADIvalue, the maximum daily highest limit is the highest. With aacesulfame-K, aspartame in combination exhibits a synergisticallyincreased sweetening power. As a result, the concentration with 40 mgfor aspartame was only selected to be half as high as the maximallypermissible daily highest limit. In order to ensure a comparability withthe other sweeteners, the concentration of aspartame was also retainedfor the remaining combinations.

After organoleptic testing, the result of the investigation is that acomplete masking of the salty taste of ORS solutions can be achieved bycombinations of the sweeteners Na-cyclamate, acesulfame-K and aspartame.By means of the combinations with the sweetener saccharin-Na, animprovement of the taste could be achieved but the masking of the saltytaste was not complete. In addition, saccharin-Na is suspected ofpromoting the growth of bladder carcinomas. In the furtherinvestigations work was only carried out with the sweeteners accordingto the invention, Na-cyclamate, acesulfame-K and aspartame.

Three sweetener combinations with the sweeteners Na-cyclamate,acesulfame-K and aspartame have been proven to be suitable for themasking of the salty taste of ORS solutions. Proceeding from the testedconcentration ratios of the combinations it was investigated whether thesame masking of taste can be achieved by a reduction in dose of thesweeteners. It was possible to reduce the concentration of thesweeteners. The final concentrations of the sweetener combinations for amasking of taste of the salty taste of ORS solutions are per dose:

Na-cyclamate/acesulfame-K 25 mg/25 mg sweetening power: 5750Na-cyclamate/aspartame 25 mg/30 mg sweetening power: 6750acesulfame-K/aspartame 20 mg/20 mg sweetening power: 8000

The sweetening power is different in all three combinations. The abilityto mask a salty taste is highest for Na-cyclamate, followed byacesulfame-K and aspartame.

Finished Preparations C and B

The finished preparations C and B with the flavours neutral, strawberryand apple-banana are combined according to the new WHO guideline (Table4).

TABLE 4 Composition of preparation C and B Constituent Concentration[g]/sachet Glucose 3.56 Sodium chloride 0.47 Potassium chloride 0.3Disodium hydrogen citrate-1,5 hydrate 0.53

It emerges from the composition that a salty taste of an aqueoussolution of the powder is to be expected by the addition of sodiumchloride and potassium chloride in a total quantity of 0.77 g per dose.In the formulation of preparation C, the sweetener aspartame and highlydisperse silicon dioxide are contained as further constituents. Onlyhighly disperse silicon dioxide is additionally contained in preparationB neutral. In preparation B strawberry, the sweetener aspartame, highlydisperse silicon dioxide, strawberry flavouring, malic acid and, as thecolourant, beetroot dry extract (betanin, E 162) have been added.Preparation B apple-banana additionally contains the sweeteneraspartame, highly disperse silicon dioxide, apple-banana flavouring,malic acid and the colourant carotin (E 160a).

With the exception of preparation B neutral, in the case of the finishedpreparations, sweeteners and flavourings are added to improve the taste.An aim of the present invention was to check whether the four finishedpreparations taste salty despite the additions for taste improvement.

It should be noted that both the preparation B and C contain sweetenerconcentrations which are far below the threshold concentrationsaccording to the invention.

The taste perception was checked in a test attempt with 12 testsubjects. The individual powder mixtures were prepared according toinstructions for application directly before the tasting. The test tookplace in a randomised and double-blind manner. The evaluation criteriaare the flavours salty, sweet and sour in the classifications ofperception very-medium-not and the odour with the classificationspleasant-neutral-unpleasant.

FIG. 1: results of the taste test of the finished preparation B withoutsweetener and flavouring.

FIG. 2: results of the taste test of the finished preparation B with thesweetener aspartame and strawberry flavouring.

FIG. 3: results of the taste test of the finished preparation B with thesweetener aspartame and apple-banana.

FIG. 4: results of the taste test of the finished preparation C withoutflavouring and with the sweetener aspartame.

The colouring of the charts is based on a traffic light principle. Theevaluation criterion which was classified as negative, for example avery salty taste of a solution, is shown in the colour red. Thecriterion which is considered satisfactory, for example a solution whichtastes medium salty, is shown in the colour amber. The criterion whichis considered positive, for example a solution which does not tastesalty, is shown in the colour green. In the case of preparation Bneutral, the salty taste of the solution was perceived most frequentlyand clearly of all the four preparations. 91.2% of the test subjectsgenerally perceived a salty taste. 58.8% of the test subjects assessedthe salty taste with “very”. Without the addition of taste correctivesin preparation B neutral, a perception of the salty taste was expectedin advance of the taste test. The result of the taste test confirms theexpectation. Additions of sweeteners and flavourings are contained inthe three remaining finished preparations. The salty taste was assessedless frequently and clearly in all three finished preparations than inpreparation B neutral. A taste improvement can be achieved byflavourings and sweeteners. The extent varies.

Taste Testing of the ORS Solutions with the Addition of SweetenerCombinations in Comparison to Finished Pharmaceutical Agents

Sodium chloride and potassium chloride are contained inter alia aseffective constituents in ORS solutions. An aqueous solution of theconstituents is perceived as salty. For the finished pharmaceuticalagents mentioned above, a perceivable salty taste has been shown in atest with test subjects. An aim of the present invention is to ascompletely as possible mask the salty taste of ORS solutions, as a saltytaste is perceived as unpleasant and can lead to compliance problems inthe therapy.

A complete masking could be achieved according to the invention withthree sweetener combinations of the sweeteners Na-cyclamate,acesulfame-K and aspartame. The results were to be confirmed in a testwith test subjects using 12 healthy test subjects. In order to be ableto make a comparable statement, the above-mentioned finishedpreparations were also included in the test. The results of the ORSsolutions with sweetener combinations are shown in FIGS. 5 to 11.Depending on the sweetener combination, the salty taste of the solutionswas assessed as “not salty” by 50 to 67% of the test subjects. Thefinished preparations B neutral and C without an addition of flavouringwere only described as “not salty” by 8% or 25%, respectively, of thetest subjects. The addition of sweetener combinations increases thepositive impression “not salty” by up to 59%.

FIG. 5: results of the taste test for the sweetener combinationacesulfame-K/Na-cyclamate.

FIG. 6: results of the taste test for the sweetener combinationaspartame/Na-cyclamate.

FIG. 7: results of the taste test of the sweetener combinationacesulfame-K/aspartame.

Osmolarity

The addition of sweeteners to ORS solutions changes the osmolarity ofthe solutions. The theoretical osmolarity is calculated at 240 mosmol/lowing to the effective constituents of the ORS solutions. The WHOrecommends a total osmolarity of 245 mosmol/l. The sweeteners in thecombinations and concentrations determined only increase the totalosmolarity of the ORS solutions slightly.

TABLE 5 Osmolarity of the ORS solutions with sweeteners Theoreticalosmolarity of Measured Quantity the total solution osmolarity Sweetenercombination [mg] [mosmol/l] [mosmol/l] Acesulfame-K/aspartame 20/20241.3 234 Acesulfame-K/Na- 25/25 242 235 cyclamateAspartame/Na-cyclamate 30/25 241.5 245

The addition of sweetening agents does not have a significant effect onthe total osmolarity of the ORS solutions. Table 5 gives the measuredosmolarities of the solutions. The recommendation of the WHO ofoptimally 245 mosmol/l is ensured.

Further sweetening agents were included in a taste testing. An additionof sugars and sugar alcohols has a substantially stronger effect on thetotal osmolarity of an ORS solution than the addition of sweeteners.Calculated to the standard concentration of 200 mg Na-cyclamate, theosmolarity values have different levels (Table 9). In addition to thetotal osmolarity of the effective constituents of the ORS solutions, thevalues are outside the recommended limits of the WHO recommendations.The quantities to be added are not to be recommended either in relationto the promotion of caries and a laxative effective. A combination ofsugars or sugar alcohols does not lead to a significant improvement inthe osmolarity.

TABLE 6 Osmolarity of sugars and sugar alcohols Theoretical SweeteningCalculated osmolarity Substance power Factor quantity [mg] [mosmol/l]Lactose 0.2 150 30000 440 Mannitol 0.4 75 15000 410 Isomalt 0.45 66.6713334 195 Glucose 0.5 60 12000 333 Sorbitol 0.6 50 10000 274 Maltitol0.9 33.33 6666 97 Saccharose 1 30 6000 88 Xylitol 1 30 6000 197 Fructose1.2 25 5000 139 Erythritol approx. 2 15 3000 123 Na-cyclamate 30 1 20010

A taste test was nevertheless carried out with the sugars and sugaralcohols. Complete dissolution took place in water and an organoleptictest took place with the calculated quantities. With maltitol,erithritol and saccharose a masking of the salty taste of the ORSsolutions could substantially be achieved. The concentrations ofsubstances were reduced to such an extent that the maximum limit of theosmolarity of 311 mosmol/l was adhered to. No masking of taste could beachieved by saccharose. For maltitol and erithritol, it wassubstantially not salty, but very sour and not sweet. The result issignificantly different compared to the addition of sweetenercombinations. The addition of sweeteners is to be preferred in each casewith regard to side-effects, osmolarity and a complete masking of thesalty taste.

Addition of Flavouring

ORS solutions taste salty because of the ingredients NaCl and KCl. TheEuropean Medicines Agency (EMEA) recommend in their “Reflection paper:Formulations of choice for the paediatric population”, flavourings,which can be added to mask certain flavours. For a salty taste, theseare the flavourings caramel, grapefruit, lemon, orange and vanilla. Itshould be checked whether a flavouring addition, in addition to theaddition of a sweetener combination, more completely masks the saltytaste of ORS solutions without the addition of a flavouring.

In a study, fruit juices were added for flavouring in order to make thetaste of ORS solutions more pleasant. The ORS solutions were diluted indifferent ratios with apple or orange juice and orange lemonade. Thetaste was perceived as more pleasant owing to the dilution. Theosmolarity of the solutions was increased by a multiple factor, however.The values neither corresponded to the requirements of the WHO with amaximum of 311 mosmol/l nor of the ESPGAN with a maximum of 250mosmol/l. A dilution with juice or lemonade is not to be recommended.ORS solutions can only be flavoured by the direct addition offlavourings.

Dry flavourings may be exclusively added to a powder mixture for ORSsolutions. The selection of a flavouring was oriented to therecommendations of the EMEA. Firstly, an orange dry flavouring was addedto the powder mixture of an ORS solution. The concentration of theorange dry flavouring of 175 mg/dose was determined in advance. Thesweetener combinations of acesulfame-K/aspartame,acesulfame-K/Na-cyclamate and aspartame/Na-cyclamate were added to theflavouring in the determined concentrations in each case. The flavouredORS solutions were tested in the framework of the taste test at thesweetener concentrations. The results are shown in FIG. 8.

FIG. 8: results of the taste test of the salty taste of the threesweetener combinations and orange dry flavouring

The salty taste of the solutions with orange flavouring was assessed,depending on the sweetener combination, as “not salty” by 67 to 75% ofthe test subjects. The result is again better than the result of thetest without a flavouring addition (50 to 67%). In a list of priority ofthe favoured solutions, of the ten test solutions, all three ORSsolutions with a sweetener combination and orange flavouring in eachcase were evaluated at the first three places.

Taste testing of the ORS solutions with the addition of sweetenercombinations and different flavourings in comparison to the preparationB apple-banana

Glucose-electrolyte solutions, so-called ORS solutions, contain NaCl andKCl inter alia as effective constituents. An active ORS solution tastessalty. After the addition of the sweetener combinationsacesulfame-K/aspartame, acesulfame-K/Na-cyclamate andaspartame/Na-cyclamate, a masking of the salty taste could besubstantially achieved. By adding an orange flavouring, the maskingcould be further improved. Further flavourings were to be tested inorder to develop a mixture that is as optimal as possible for an ORSsolution with a masked salty taste and pleasant taste. The flavouringslemon, orange, pineapple and raspberry were selected for a taste test.The concentrations of the flavourings for the test were determined inadvance. The flavourings were tested with each sweetener combination ina taste test with 12 healthy test subjects. The finished preparation,preparation B apple-banana was included in the test as it was assessedas best in the previous tests of all finished preparations and is alsoflavoured. In total, 22 solutions were tasted. The results of the tastetest are shown in FIGS. 9 to 13.

The salty taste of the ORS solutions is substantially masked by theaddition of all the flavourings. The assessment “not salty” differsbetween 52.7 and 83.3% depending on the flavouring. The results relateto the assessment of the salty taste of all sweetener combinations ofeach individual flavouring to determine a preference for one flavouring.

FIG. 9: results of the taste test of all sweetener combinations with theflavouring addition pineapple.

FIG. 10: results of the taste test of all sweetener combinations withthe flavouring addition lemon.

FIG. 11: results of the taste test of all sweetener combinations withthe flavouring addition orange.

FIG. 12: results of the taste test of all sweetener combinations withthe flavouring addition raspberry.

FIG. 13: results of the taste test of the finished preparation Bapple-banana.

The test subjects were requested to select a favourite mixture perflavouring group from the three different sweetener combinations and toname their three overall favourites of all 22 solutions at the end.Despite a total assessment of only 52.8% for “not salty” for theflavouring raspberry, the ORS solutions were assessed as best. There isno complete masking of the salty taste. The overall taste impression ofthe ORS solutions is decisive for a positive evaluation in contrast toan evaluation of an individual criterion. The overall favourites wereevaluated with the aid of an accumulative score. The flavouringsraspberry and lemon were assessed as best.

TABLE 10 Results of the flavouring taste test of the ORS solutionsPriority Not Osmolarity pH lists Score Flavouring salty (mosmol/l) valueplace (accumulative) Raspberry 52.8% 235 5.32 1 20 Lemon 61.1% 237 5.392 20 Orange 80.6% 228 5.40 3 13 Preparation B   75% 244 4.95 6 3apple-banana Pineapple 66.7% 233 5.36 7 3

The addition of flavourings to the effective constituents of the ORSsolutions and the sweetener combinations does not lead to a rise in theosmolarity. The measured osmolarities of the solutions are all in therange of the WHO recommendation of 245 mosmol/l. They are overallslightly lower (Table 10). The pH of the ORS solutions is in theslightly acid range at 5.40 in all our own formulations (Table 10). Ofall the 22 solutions, the mixtures of the sweetener combinationsacesulfame-K/aspartame with the flavourings raspberry or lemon wereassessed as best. The individual results are shown in FIGS. 14 and 15.The ORS solution with raspberry flavouring and acesulfame-K/aspartamewas assessed as being in the first place. The score is 14 points. TheORS solution with lemon flavouring and acesulfame-K/aspartame, with ascore of 12 points, is in second place.

FIG. 14: results of the taste test of the sweetener combinationacesulfame-K/aspartame with the flavouring addition raspberry

FIG. 15: results of the taste test of the sweetener combinationacesulfame-K/aspartame with the flavouring addition lemon

The evaluations of the individual mixtures differ from the evaluation ofthe total flavouring groups. The evaluation of “not salty” at 75.0%compared to 52.8% of the total flavouring group is striking, inparticular. In the mixture with lemon flavouring, the differences areeven clearer: “not salty” 66.7% compared to 61.1%, “medium sweet” 83.4%compared to 66.7%, “not sour” 66.7% compared to 66.7%, “pleasant odour”66.7% compared to 55.5% and “flavouring OK” 91.7% compared to 72.2%.

In total, the mixtures of sweeteners acesulfame-K and aspartame with theflavouring additions raspberry or lemon were assessed as best of all theformulations.

The optimal composition for ORS solutions is:

NaCl 0.47 g, KCl 0.3 g, glucose-monohydrate 3.56 g, Na-monohydrogencitrate-1,5-hydrate 0.53 g, acesulfame-K 20 mg, aspartame 20 mg,raspberry flavouring 150 mg or lemon flavouring 165 mg.

1. A method for masking the salty taste of a composition, the methodcomprising using at least one sweetener from the group of sodiumcyclamate, aspartame or acesulfame potassium for masking the salty tasteof a composition.
 2. The method according to claim 1, wherein a mixtureof two or three sweeteners is used for masking the taste.
 3. The methodaccording to claim 1, wherein the concentration of the sweeteners basedon the salt content is calculated by the following formula:relative sweetening power of the sweetener×mass of the sweetener[inmg]>5,000 based on a salt content of the composition of 0.7 to 0.8,preferably 0.77 g.
 4. The method according to claim 3, whereinNa-cyclamate is used in a concentration of 22 to 28, preferably 26% byweight based on the salt content of the composition.
 5. The methodaccording to claim 3, wherein acesulfame potassium is used in aconcentration of 3.3 to 4.5, preferably 3.9% by weight, based on thesalt content of the composition.
 6. The method according to claim 3,wherein aspartame is used in a concentration of 3.3 to 4.5, preferably3.9% by weight, based on the salt content of the composition.
 7. Themethod according to claim 1, wherein a mixture of two or three of thesweeteners according to claim 1 is used, wherein the concentration ofthe sweetener mixture based on the salt content is calculated asfollows:rel. sweetening power Na-cyclamate×mass Na-cyclamate[in mg]+rel. sweetening power aspartame×mass aspartame[in mg]+rel. sweetening power acesulfame-K×mass acesulfame-K[in mg]>5,000 basedon a salt content of the composition of 0.7 to 0.8, preferably 0.77 g.8. The method according to claim 1, wherein the following sweetenercombinations are used: Na-cyclamate/acesulfame-K Na-cyclamate/aspartame,or acesulfame-K/aspartame.
 9. The method according to claim 8, whereinthe following concentrations (in % by weight) based on the salt contentof the composition are used in each case: 3.2/3.2 3.9/3.2 2.6/2.6 10.The method according to claim 1, wherein the taste of NaCl and/or KCl isto be masked.
 11. The method according to claim 1, wherein thecomposition is a pharmaceutical composition, a foodstuff or a foodsupplement.
 12. The method according to claim 11, wherein thepharmaceutical composition is an electrolyte composition.
 13. The methodaccording to claim 11, wherein the foodstuff or the food supplement isan electrolyte drink.
 14. A salt-containing composition, which containsat least one sweetener from the group of sodium cyclamate, aspartame oracesulfame potassium, wherein the quantity of sweetener is suitable formasking the salty taste of the composition.
 15. The compositionaccording to claim 14, wherein a mixture of two or three sweeteners isused to mask the taste.
 16. The composition according to claim 14 or 15,wherein the concentration of the sweeteners based on the salt content iscalculated by the following formula:relative sweetening power of the sweetener×mass of the sweetener[inmg]>5,000 based on a salt content of the composition of 0.7 to 0.8,preferably 0.77 g.
 17. The composition according to claim 16, whereinNa-cyclamate is used in a concentration of 22 to 28, preferably 26% byweight, based on the salt content of the composition.
 18. Thecomposition according to claim 16, wherein acesulfame potassium is usedin a concentration of 3.3 to 4.5, preferably 3.9% by weight, based onthe salt content of the composition.
 19. The composition according toclaim 16, wherein aspartame is used in a concentration of 3.3 to 4.5,preferably 3.9% by weight, based on the salt content of the composition.20. The composition according to claim 14, wherein a mixture of two orthree of the sweeteners according to claim 14 is used, wherein theconcentration of the sweetener mixture based on the salt content iscalculated as follows:rel. sweetening power Na-cyclamate×mass Na-cyclamate[in mg]+rel. sweetening power aspartame×mass aspartame[in mg]+rel. sweetening power acesulfame-K×mass acesulfame-K[in mg]>5,000 basedon a salt content of the composition of 0.7 to 0.8, preferably 0.77 g.21. The composition according to claim 14, wherein the followingsweetener combinations are used: Na-cyclamate/acesulfame-KNa-cyclamate/aspartame, or acesulfame-K/aspartame.
 22. The compositionaccording to claim 21, wherein the following concentrations (in % byweight) based on the salt content of the composition are used in eachcase: 3.2/3.2 3.9/3.2 2.6/2.6
 23. The composition according to claim 14,wherein the salt comprises NaCl and/or KCl or consists thereof.
 24. Thecomposition according to claim 14, wherein the composition is apharmaceutical composition, a foodstuff or a food supplement.
 25. Thecomposition according to claim 24, wherein the pharmaceuticalcomposition is an electrolyte composition.
 26. The composition accordingto claim 24, wherein the foodstuff or the food supplement is anelectrolyte drink.
 27. The composition according to claim 24, whereinthe pharmaceutical composition is an ORS (oral rehydration salt)preparation.
 28. The composition according to claim 14, which has thefollowing ingredients: Constituent Concentration [g]/Single dose Glucose3.56 Sodium chloride 0.47 Potassium chloride 0.3 Disodium hydrogencitrate-1,5 hydrate 0.53